Novel Angiogenesis Markers as Long-Term Prognostic Factors in Patients With Renal Cell Cancer.

OBJECTIVE: To evaluate Ang-2 expression alone and in combination with expression of cell proliferation and cell survival markers (MIB-1 and Bcl-2) and angiogenesis markers (VEGFR3 and CD31), and the associations of these markers with renal cell cancer (RCC) in long-term survival. PATIENTS AND METHODS: Our study included 224 patients with RCC who were treated before the availability of antiangiogenic agents between 1985 and 1995, at the Pirkanmaa Hospital District in Finland. All tumor samples were reclassified and reevaluated by an experienced uropathologist, and parallel tissue microarrays (TMA) were performed for immunohistochemical analysis. Kaplan-Meier's survival estimation method and Cox proportional hazards models were used for survival analysis. RESULTS: The percentage of Ang-2 expression in the tumor area varied from 0.07 to 25.65. Ang-2 expression was significantly associated with the tumor grade and stage, as well as the MIB-1, Bcl-2, and VEGFR3 expression (P = .042, P = .019, P = .039, P = .013, and P = .005, respectively). The highest Ang-2 expression predicted better survival, P < .05. High Bcl-2 and low MIB-1 expression combined with Ang-2 expression was associated with better survival. Multivariate analysis showed poorer survival in patients with low Ang-2 or high MIB-1 expressions: HR 1.89, 95% CI 1.16 to 3.08, P = .010 and HR 2.20, 95% CI 1.36 to 3.54, P = .001, respectively. CONCLUSIONS: Very high Ang-2 expression was associated with better survival in patients with RCC. Ang-2 expression correlated with tumor stage and grade, but it was still an independent prognostic factor in a multivariate analysis.

Combined Angiogenesis and Proliferation Markers' Expressions as Long-Term Prognostic Factors in Renal Cell Cancer.

OBJECTIVES: The aim of this study was to evaluate the expression of MIB-1, BCL-2, VEGFR3, and CD31 and their associations with long-term survival in patients with renal cell cancer (RCC). PATIENTS AND METHODS: This study consisted of 224 RCC patients who underwent radical nephrectomy from 1985 to 1995. Follow-up continued for up to over 20 years. MIB-1 and BCL-2 expression were analyzed alone, and additionally, the expression of MIB-1, BCL-2, VEGFR3, and CD31 were combined in pairs using the following groups: low/low, low/high, high/low, and high/high. RESULTS: Low BCL-2 expression (hazard ratio [HR], 2.16; 95% confidence interval [CI], 1.42-3.31; P < .001 compared with high BCL-2 in univariate analysis) and high MIB-1 expression (HR, 2.05; 95% CI, 1.32-3.19; P = .001 in multivariate analysis) were found to associate for poorer survival in RCC. In multivariate analysis, the combination of high MIB-1/low BCL-2 was associated with poor survival compared with low MIB-1/high BCL-2 (HR, 3.20; 95% CI, 1.66-6.17; P = .001), and the combination of low VEGFR3/high CD31 was associated with poor survival (HR, 2.48; 95% CI, 1.29-4.78; P = .007) compared with high VEGFR3/high CD31. CONCLUSIONS: Compared with high BCL-2 expression in combination with low or high MIB-1, VEGFR3, or CD31 expression, low BCL-2 expression in combination with low or high MIB-1, VEGFR3, or CD31 expression has poorer survival in the long-term follow-up of patients with RCC. Analysis of MIB-1, BCL-2, VEGFR3, and CD31 expression might be a useful additional marker to tailor the follow-up of RCC patients.

Development of renal cell carcinoma (RCC) diagnostics and impact on prognosis.

OBJECTIVE: To evaluate imaging methods and prognoses between small renal cell carcinomas (RCCs) and larger tumours according to the era of diagnostics. PATIENTS AND METHODS: In all, 784 consecutive patients diagnosed with RCC between 1964 and 1997 at the Pirkanmaa Hospital District in Finland were included. Patients were divided into two groups: tumours of ≤3.0 and >3.0 cm in diameter. Prognosis was analysed according to the era of diagnostics: (i) pre-computed tomography (CT) and pre-ultrasound (US), (ii) US era and (iii) CT era. RESULTS: Small tumours became more common: in the pre-CT and pre-US era, only 4.4% of tumours were small; however, in the CT era 16% were small tumours. More diagnostic methods were used in studying small tumours. CT proved to be the most reliable method, although it was actually better at diagnosing large tumours. Relapses occurred less frequently among patients with small tumours; more than half of the tumours that developed distant metastases (16.0%) already evinced them at the time of diagnosis. There were no relapses after 14 years of follow-up among small tumours, whereas large tumours relapsed within that time. RCC was the cause of death in 14.9% of patients with small tumours vs 50.7% with large tumours. The best prognosis was among patients with small tumours diagnosed with CT. CONCLUSION: Among patients with small tumours, prognosis has improved along with better diagnostics, although some showed relapse during a surveillance period of up to 14 years.

Changes in symptoms of renal cell carcinoma over four decades.

OBJECTIVE: To determine whether there has been a change in typical symptoms of renal cell carcinoma (RCC), by evaluating the symptoms of patients diagnosed during four decades, as although the increasing incidence of a diagnosis of incidental RCC has been widely reported, the change in other symptoms has not. PATIENTS AND METHODS: The study included RCC cases diagnosed in the Pirkanmaa Hospital District between 1964 and 1997. The original medical records of 970 patients with 982 RCC tumours were analysed. Primary symptoms were recorded and changes were analysed in three groups, i.e. diagnoses made before 1980, in the 1980s and in the 1990s. Symptoms were also analysed according to stage, tumour class, gender and age. RESULTS: The incidence of haematuria (P < 0.01) and an increased erythrocyte sedimentation rate (P < 0.001) decreased, but there was no change in other symptoms. Incidental diagnoses increased from 12% to 19% (P < 0.01). Less chronic or systemic symptoms were noted more recently. Stage and tumour class were highly correlated with symptoms: systemic symptoms increased (24% in stage I to 72% in stage IV, a highly statistically significant increase) and asymptomatic tumours became rarer (27% in stage I to 8% in stage IV, again a highly significant increase) with increasing stage. Haematuria was more common in male patients, anaemia and flank pain in women. Elderly patients were more often asymptomatic than younger patients, with 70-79-year-olds being the least symptomatic. CONCLUSIONS: Incidental cases of RCC have recently become more common. Haematuria, hypersedimentation, chronic and systemic symptoms have decreased. Stage, tumour class, gender and age are correlated with symptoms.

Prognostic factors and long-term survival in renal cell cancer patients.

OBJECTIVE: The long-term survival of renal cell cancer (RCC) patients is not reported in the recent literature. This study evaluated the significance of known clinical prognostic factors and long-term survival in a large centrally treated Finnish RCC population. MATERIAL AND METHODS: In 948 patients diagnosed between 1964 and 1997 the relative overall survival (OS) was calculated up to 25 years by Bayesian analysis and the life-table method. The effect of gender, age, cancer stage, TNM (tumour, node, metastasis) class, Fuhrman's grade, symptoms and year of diagnosis was studied. RESULTS: Women and patients aged 40-49 years had better survival. Stage, TNM class and grade proved relevant for prognosis. The relative 5-year overall survival was 88%, 63%, 65% and 15% in stages I-IV, respectively. Asymptomatic patients had better survival, their median survival being 8.1 years as against 9.1 years in patients with local symptoms and only 1.7 years in patients with systemic symptoms. The year of diagnosis was not significant in prognosis. CONCLUSIONS: The most important explanatory factors were stage, age and clinical presentation of the tumour. RCC patients showed diminishing overall survival in the follow-up, with no plateau; almost 57% of patients developed local recurrence or distant metastases even after a very long disease-free interval.